The LottoNL-Jumbo fast man upstaged Elia Viviani (Quick-Step Floors) and Andre Greipel (Lotto Soudal) to take his fifth win of the season and perhaps a claim as the best sprinter so far this season.
"I felt very strong, the team is very strong," Groenewegen said. "The stage was fairly easy but it was a hard sprint with a small climb towards the end.
"It's really nice to beat the other favourites. The finale was going very hard and I won so that's very good. Today was the biggest chance for a bunch sprint so it was good that we managed to do it today.
"All races are important but this is my first win on Paris-Nice so it is special. Tomorrow is another chance but it's harder than today. We'll see how it goes"
Arnaud Démare (Groupama-FDJ) finished fifth to hold on to his overall lead ahead of Gorka Izagirre (Bahrain-Merida) and Christophe Laporte (Cofidis).
"It was slow in the beginning because we knew there was bound to be a bunch sprint," Démare said. "After a while, my team-mates worked so that we could take part in the intermediate sprint and then the finale was pretty fast.
"I only have myself to blame in the final sprint. I waited and waited and by the time I went, it was too late. Keeping the yellow jersey was a consolation of sorts.
"Tomorrow could be another chance for the sprinters even if it's much harder and we'll see how it goes. Paris-Nice is always a race in which I give my best. I'm strong now but I hope to get even stronger later in the season."
The race rolled along before Demare strengthed his hold on the race lead after winning the first intermediate sprint ahead of Alaphillipe.
With 100km covered Thomas De Gendt (Lotto Soudal) led Manuele Boaro (Bahrain-Merida), Tiago Machado (Katusha), Oliver Naesen (AG2R), Anthony Delaplace (Fortuneo-Samsic) and Lars Boom (LottoNL-Jumbo) on a break.
Nervous about the strength of the selection, Groupama-FDJ, Cofidis and Quick-Step Floors led a frantic chase and four of the escapees were reined in 22km later while Machado and Boaro stuck to their guns to build a three-minute lead.
Machado beat Boaro in the second intermediate sprint while the peloton played cat and mouse with the duo until the last four kilometres when it finally reeled them in.
Thomas De Gendt (Lotto- Soudal), Tim Declercq (Quick-Step Floors) and Tom Leezer (LottoNL-Jumbo) took turns at the front of the bunch, working for their sprinters Greipel, Viviani and Groenewegen.
UAE Team Emirates leader Rui Costa abandoned early on Stage 2 suffering from the effects of two crashes during the opening stage.
The 210km third stage from Bourges to Chatel-Guyon in the Puy-de-Dome region should also feature a sprint finish or a narrowed selection.